Ajay K. Wakhloo

Alteration of hemodynamics in aneurysm models by stenting: Influence of stent porosity

Recent developments in minimally invasive approach to cerebrovascular diseases include the placement of stents in arteries for treatment of aneurysms. Preliminary clinical observations and experimental studies have shown that intravascular stents traversing the orifice may lead to thrombosis and subsequent occlusion of the aneurysm. The alterations in vessel local hemodynamics due to the introduction of a stent are not yet well understood. We investigated changes in local hemodynamics resulting from stent implantation. Pulsatile flow patterns in an experimental flow appraratus were visualized using laser-induced fluorescence of rhodamine dye. The test cells were constructed in a rectangular shape to facilitate an undisturbed longitudinal view of flow patterns in parent vessel and aneurysm models with and without porous stents. Woven nitinol stents of various porosities (76%, 80%, 82%, and 85%) were investigated. The selected fluid dynamic similarity parameters (Reynolds and Womersley numbers) represented conditions usually found in high-flow, larger arteries in humans (such as the carotid artery) and low-flow, smaller arteries (such as the vertebral artery). The mean Reynolds number for the larger arteries was 180, with maximum/minimum values of 490/−30 and the Womersley number was 5.3. The mean Reynolds number for the smaller arteries was 90, with maximum/minimum values of 230/2, and the Womersley number was 2.7. For the larger arteries modeled, placement of a stent of the lowest porosity across the aneurysm orifice resulted in reduction of aneurysmal vortex speed and decreased interaction with parent vessel flow. For smaller arteries, a stent of the same porosity led to a substantial reduction of parent vessel/aneurysmal flow interaction and the appearance of a nonrecirculating crescent of fluid rich in rhodamine dye in the aneurysm dome. Our results can help explainin vivo thrombus formation within an aneurysm after placement of a stent that is compatible with local hemodynamics.

Stenting and secondary coiling of intracranial internal carotid artery aneurysm: technical case report.

OBJECTIVE AND IMPORTANCE Endovascular stents have been successfully used in the treatment of fusiform and dissecting aneurysms of the peripheral circulation and extracranial carotid and vertebral arteries. Technical limitations related to the inability to navigate the stent and the delivery system through tortuous vascular segments has limited their application with intracranial lesions. Availability of new flexible and pliable stent systems might overcome these difficulties. CLINICAL PRESENTATION A 49-year-old woman presented with a dissecting pseudoaneurysm of the horizontal portion of the petrous internal carotid artery that increased in size, as revealed by serial angiographic studies. INTERVENTION The aneurysm was treated by deploying a new flexible stent across the aneurysm neck and by then packing the aneurysm sac with Guglielmi detachable coils that were delivered by a microcatheter positioned through the stent struts into the aneurysm lumen. CONCLUSION New flexible stents can be used to treat intracranial internal carotid artery aneurysms in difficult-to-access areas, such as the horizontal petrous segment. The stent may disrupt the aneurysm inflow tract, thereby inducing stasis and facilitating intra-aneurysmal thrombosis. In addition, the stent acts as an endoluminal scaffold to prevent coil herniation into the parent artery, which allows tight packing of even wide-necked and irregularly shaped aneurysms. The stent may also serve as a matrix for endothelial growth. We think this new generation of flexible stents and the use of this described technique will usher in the next era of endovascular management of intracranial aneurysms.

Particle image velocimetry assessment of stent design influence on intra-aneurysmal flow.

AbstractEndovascular stenting appears to be an appealing treatment modality to selected complex intracranial aneurysms. However, stents currently used for endovascular treatment are not specifically designed for the cerebrovasculature. Stent parameters, such as porosity and filament size, have to be carefully optimized for long-term successful treatment. We investigated the influence of the stent filament size on the intra-aneurysmal flow dynamics in a sidewall aneurysm model in vitro. Three helical stents with 76% porosity but different filament sizes of 178, 153, and 127 μm were studied using particle image velocimetry. Twenty-four pulsatile flow conditions were investigated. The results show that stenting significantly reduces intra-aneurysmal vorticity and the mean circulation inside the aneurysm is reduced to less than 3% of its value before stenting. For constant porosity, a further reduction of the mean circulation, up to 30% can be obtained by reducing the filament diameter. For a constant Womersley number, this further reduction is accentuated with increase in the peak Reynolds number. Further reduction in the mean circulation inside the aneurysm was not achieved for the 127 μm stent. With further reduction in filament diameter, the helical stent filaments positioned against the aneurysm neck started wavering with the flow transferring added momentum into the aneurysm. For stents of smaller filament diameter, a supporting ultrastructure is required.

Identification of Patients at Risk for Periprocedural Neurological Deficits Associated With Carotid Angioplasty and Stenting

BACKGROUND AND PURPOSE Transient or permanent neurological deficits can occur in the periprocedural period following carotid angioplasty and stenting (CAS), presumably due to distal embolization and/or hemodynamic compromise. We performed this study to identify predictors of neurological deficits associated with carotid angioplasty and stent placement. METHODS We reviewed medical records and angiograms in a consecutive series of patients who underwent CAS for symptomatic or asymptomatic cervical internal carotid artery stenosis from June 1996 through December 1998. Using logistic regression analysis, we evaluated the effect of demographic, clinical, intraprocedural, and angiographic risk factors on subsequent development of periprocedural neurological deficits. Periprocedural neurological deficits were defined as new or worsening transient or permanent neurological deficits that occurred during or within 48 hours of the procedure. RESULTS A total of 111 patients (mean age 68.2+/-9.1 years) who underwent CAS for asymptomatic (n=54) or symptomatic (n=57) stenoses were included in this study. A total of 14 periprocedural neurological deficits (13%) were observed either during (n=4) or after (n=10) the procedure. Three identified variables were independently associated with periprocedural neurological deficits: symptomatic lesion (OR 8.3, 95% CI 1.6 to 42.6), length of stenotic segment >/=11.2 mm (OR 5.2, 95% CI 1.2 to 22.5), and absence of hypercholesterolemia (OR 5.4, 95% CI 1.4 to 20.9). Other variables, including age and degree of stenosis (defined by NASCET criteria), were not associated with periprocedural neurological deficits. CONCLUSIONS A combination of clinical and angiographic variables can be used to identify patients at risk for periprocedural neurological deficits after CAS. Such identification may help in selection of patients who may benefit from novel pharmacological and mechanical preventive approaches.

Temporary balloon protection as an adjunct to endosaccular coiling of wide-necked cerebral aneurysms: technical note.

OBJECTIVE We present an endovascular technique for treating wide-necked cerebral aneurysms using Guglielmi detachable coils (Target Therapeutics, Fremont, CA) and simultaneous temporary balloon protection. The temporary balloon serves as a mechanical external force to mold the microcoils away from the parent artery. METHODS Two illustrative cases of wide-necked cerebral aneurysms treated with Guglielmi detachable coils and a temporary balloon are presented. Emphasis is placed on the technical aspects of the approach, with several variations. The first case involves a left posterior cerebral artery aneurysm at the P1/P2 segment, and the second case involves a left paraclinoid internal carotid artery aneurysm. Both patients suffered from subarachnoid hemorrhage, but neither was a candidate for craniotomy. In each case, the coils, when used alone, protruded into the parent artery and were therefore removed. Then a temporary balloon was inflated for mechanical protection during coil deployment. RESULTS The use of simultaneous temporary balloon protection allowed more dense intra-aneurysmal coil packing, especially in the neck, without parent artery compromise, than did the use of Guglielmi detachable coils alone. CONCLUSION Endovascular treatment of wide-necked cerebral aneurysms can be facilitated by simultaneous temporary balloon protection.

Complex-shaped platinum coils for brain aneurysms: higher packing density, improved biomechanical stability, and midterm angiographic outcome.

BACKGROUND AND PURPOSE: Five to 60% of coiled brain aneurysms recanalize, generally because of coil compaction. In vitro exclusive use of complex-shaped coils allows better packing of the aneurysmal sac and the neck as compared with helical coils. We report a single-center, prospective study using complex coils. Safety, packing density, and recanalization rate were evaluated. MATERIALS AND METHODS: Seventy-seven aneurysms were embolized using complex coils alone. Aneurysms had a volume of 265 mm3 (diameter: 7.1 ± 3.3 mm) and a neck size of 4.1 ± 1.8 mm (range: 1.5–12 mm). Average follow-up available in 31 patients was 10.5 ± 7.6 months (range: 3–36 months). Primary angiographic endpoints included aneurysmal recanalization and (re)rupture. Primary adverse events included stroke or death. RESULTS: Complete or near-complete occlusion was achieved in all of the aneurysms but required balloon assistance in 24.6%. The packing density was computed as 37% ± 13%. No rerupture was observed during the follow-up interval. Recanalization was seen in 4 (12.9%) of 31. Two basilar tip aneurysms underwent a safe and complete recoiling. Periprocedural nondevice-related neurologic deficits were seen in 2 (2.9%) of 69 patients. CONCLUSIONS: The use of complex-shaped coils allows higher packing density, which may improve the recanalization rate. Basilar tip aneurysms remain a challenge.

Endovascular Treatment of Experimental Aneurysms with Liquid Polymers: The Protective Potential of Stents

Liquid polymers have previously been used to treat experimental and human aneurysms. However, the delivery of a liquid embolic material into the cerebral circulation involves a high risk of irreversible vessel occlusion and stroke. To evaluate methods for the safe and effective treatment of experimental aneurysms with liquid polymer injection, we tested four different techniques to deliver cellulose acetate polymer (CAP) or N-hexyl-cyanoacrylate into canine side-wall carotid artery aneurysms. The animals were observed for 1 to 10 weeks after treatment. Two aneurysms were treated without protection of the distal circulation, one with CAP and another with N-hexyl-cyanoacrylate. In four cases, an angioplasty balloon was inflated within the parent artery during endosaccular injection of CAP. In two of these cases, the balloon was placed adjacent to the aneurysm orifice, resulting in simultaneous occlusion of both the aneurysm and the parent artery, and in the other two cases, the balloon was positioned proximal to the aneurysm, resulting in temporary flow arrest. Three aneurysms were treated with either CAP or N-hexyl-cyanoacrylate after implantation of a balloon-expandable tantalum stent within the parent artery across the aneurysm orifice. Complete angiographic obliteration was achieved in all but one case. One aneurysm ruptured. Another partially occluded aneurysm reopened 10 weeks after treatment. In all cases treated without stents, distal migration of the polymer resulted in either stenosis or occlusion of the parent arteries. The combination of stent implantation and polymer injection resulted in permanent aneurysm occlusion without detectable polymer migration. An intravascular stent deployed within the parent artery across the aneurysm orifice acted as a safety net during endosaccular polymer injection by allowing blood to flow from the aneurysm cavity while preventing distal migration of liquid polymer.

Angiogenesis is confined to the transient period of VEGF expression that follows adenoviral gene delivery to ischemic muscle

Therapeutic angiogenesis involves the introduction of exogenous growth factor proteins and genes into ischemic tissues to augment endogenous factors and promote new vessel growth. Positive results from studies in animal models of peripheral arterial disease (PAD) and coronary artery disease over the past decade have supported the implementation of clinical trials testing vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) proteins and genes. Although several clinical trials reported positive results, others have been disappointing and results of a recent Phase II trial of VEGF delivered by adenovirus (the RAVE trial) were negative. It has been suggested that the duration of gene expression following delivery by adenovirus may be insufficient to produce stable vessels. Here we present direct evidence in support of this using the rabbit ischemic hindlimb model injected with adenovirus encoding VEGF165. Immunohistology indicated an activation of endothelial cell cycling and proliferation 2–3 days after VEGF delivery that coincided closely with transient VEGF expression. Ki-67-positive endothelial nuclei were evident at high levels in capillaries and large vessels in muscles from treated animals. Angiography indicated increased density of both large and small vessels in Ad-VEGF-treated muscle at 1 week, but no significant differences thereafter. The early burst of endothelial proliferation was accompanied by increased nuclear fragmentation and condensation in VEGF-treated muscles, suggesting coincident apoptosis. No further endothelial cell proliferation took place after 1 week although there was still evidence of apoptosis. The results suggest that angiogenesis is confined to the short period of VEGF expression produced by adenovirus and early gains in collateralization rapidly regress to control levels when VEGF production ceases.

Mechanical Characterization of Thromboemboli in Acute Ischemic Stroke and Laboratory Embolus Analogs

BACKGROUND AND PURPOSE: Mechanical behavior of the thromboembolus is one of the key factors that determine the efficacy of thrombectomy devices for revascularization in AIS. We characterized the mechanical properties and composition of thromboemboli from clinical cases and compared them with commonly used EAs. MATERIALS AND METHODS: Thromboemboli were obtained from patients with AIS by using aspiration devices and from carotid atherosclerotic plaques harvested during endarterectomy. In the laboratory, common EAs were created by varying blood donor species (human, porcine, and bovine), thrombin concentration, and presence of barium sulfate. Stiffness and elasticity of the specimens were measured with DMA. Scanning electron microscopy and histology were used to investigate the ultrastructure and composition of all specimens. RESULTS: Red thromboemboli from patients composed mainly of fibrin and erythrocytes were much softer than the calcified and cholesterol-rich material. Of the EAs created in the laboratory, those made from bovine blood presented the highest stiffness that was independent of thrombin concentration. Addition of thrombin increased the stiffness and elasticity of human and porcine EAs (P < .05). The presence of barium sulfate significantly reduced the elasticity of all EAs (P < .05). CONCLUSIONS: Endovascular device testing and development requires realistic EAs. The stiffness and elasticity of the cerebral thromboemboli analyzed in this study were closely matched by recalcified porcine EAs and thrombin-induced human EAs. Stiffness of the thrombus extracted from carotid endarterectomy specimens was similar with that of the thrombin-induced bovine and porcine EAs.

Retrieval of a Guglielmi detachable coil after unraveling and fracture: case report and experimental results.

Unraveling and fracture of electrolytically detachable coils (Guglielmi detachable coils) may occur during treatment of intracerebral aneurysms. Retrieval of the detached coil is difficult using existing snare technology, and the intraluminal coil may cause parent vessel thrombosis or distal embolization. We report a case of unraveling and fracture of a Guglielmi detachable coil that was successfully retrieved using a dual guidewire technique. The technique was evaluated in an in vitro model using 10 coils of varying sizes and diameters, and allowed successful coil retrieval in all trials.